Three-year safety and efficacy data on the use of finasteride in the treatment of benign prostatic hyperplasia

doi:10.1016/0090-4295(94)90068-X

Urology

Volume 43, Issue 3, March 1994, Pages 284-294

https://doi.org/10.1016/0090-4295(94)90068-X Get rights and content

Abstract

Objective. To assess the long-term safety and efficacy of finasteride in the treatment of symptomatic benign prostatic hyperplasia in patients treated with finasteride 5 mg for thirty-six months.

Methods. Two large multicenter studies were used. Patients were randomly assigned to treatment with finasteride, 1 or 5 mg, or placebo for twelve months. After completing twelve months of therapy, patients were invited to enter an open extension to the study in which all patients received finasteride 5 mg. Urinary symptoms, urinary flow rate, prostate volume, and serum concentrations of prostate-specific antigen and dihydrotestosterone were measured periodically during the study.

Results. After thirty-six months of treatment with finasteride 5 mg, prostate volume was reduced from baseline by approximately 27 percent, maximum urinary flow rate improved by approximately 2.3 mL/second, and symptom scores improved by 3.6 points. Forty-two percent of patients had a 30 percent or greater decrease in prostate volume, 40 percent of patients showed an increase of 3 mL/second or more in maximum urinary flow rate, and 48 percent of patients experienced a 50 percent or greater improvement in symptom scores. Finasteride was well tolerated and there was no evidence of increased adverse experiences with increased duration of treatment.

Conclusions. The excellent safety profile and sustained clinical efficacy, over thirty-six months, of daily treatment with finasteride 5 mg recommend finasteride as a low-risk medical option for the treatment of symptomatic benign prostatic hyperplasia.

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The role of benign prostatic hyperplasia treatments in ejaculatory dysfunction
2021, Fertility and Sterility
Ejaculatory dysfunction is not only psychologically distressing but can become a significant obstacle for men who wish to conceive. Dysfunction comes in the form of anejaculation, reduced ejaculation, retrograde ejaculation, painful ejaculation, or premature ejaculation. Most treatments for lower urinary tract symptoms related to benign prostatic hyperplasia, which commonly occurs in aging men, carry significant risks of absent, reduced, or retrograde ejaculation. This review focuses on such risks that accompany both the medical and surgical management of lower urinary tract symptoms/benign prostatic hyperplasia and how these risks impact male fertility.
Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats
2021, Journal of Sexual Medicine
Citation Excerpt :
5ARIs not only cause de novo ED, but also increase the severity of pre-existing ED.8 More importantly, although the incidence of ED is usually reported to decline after 1 year of exposure, 30%–50% remain persistent after cessation of therapy, which is a serious complication of 5ARI treatment.5,9–12 The mechanisms underlying the cause and persistence of ED and characteristics of the susceptible patients are not fully understood.
Effects of human umbilical cord blood (HUCB) as a valuable source for stem cell-based therapies have not been studied in persistent post-5-alpha reductase inhibitors (5ARI) erectile dysfunction (PPED).
To determine the effect of intracavernosal injection of HUCB mononuclear cells (MNCs) on ED associated with dutasteride treatment.
Twenty five adult male Sprague-Dawley rats were divided into 5 groups (n = 5 per group): (i) control, (ii) 8-week dutasteride (0.5 mg/kg/day, in drinking water), (iii) 12-week dutasteride, (iv) 8-week dutasteride+HUCB-MNCs (1 × 10⁶) and (v) 12-week dutasteride+HUCB-MNCs. HUCB-MNCs were administered intracavernosally after eight weeks of dutasteride treatment. Experiments were performed at 4 weeks following the injection of HUCB-MNCs. Erectile responses and isometric tension of corpus cavernosum (CC) were measured. The protein expressions of phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), hypoxia-inducible factor (HIF)-1α and smooth muscle/collagen contents in penile tissue were evaluated by Western blotting, immunohistochemistry, and Masson's trichrome staining, respectively.
In vivo erectile function, in vitro relaxant and contractile responses of CC, protein expression and localization of PDE5, eNOS, nNOS, HIF-1α, and smooth muscle content in penile tissue.
Erectile responses in the dutasteride-treated groups were significantly decreased compared with controls (P < .001), persisting after 4-wk of washout. HUCB-MNCs restored diminished intracavernosal pressure responses, acetylcholine-, sodium nitroprusside-, sildenafil-induced relaxations, and increased phenylephrine and electrical field stimulation (EFS)-induced contractions. Decreased EFS-induced relaxations in dutasteride-treated groups were not restored by HUCB-MNCs. Increased PDE5 and reduced nNOS expressions in dutasteride groups were restored by HUCB-MNCs in the 12-week dutasteride group. eNOS and HIF-1α protein expression and serum total and free testosterone levels were similar among groups. HUCB-MNCs reversed the decreased smooth muscle/collagen ratio in dutasteride-treated tissues. There was a significant increase in PDE5 and HIF-1α staining in 8-week dutasteride animals.
This study demonstrates the corrective potential of HUCB-MNCs on some persistent structural and functional deterioration caused by 5ARI treatment in rats, which may encourage further evaluation of HUCB-MNCs in men with PPED.
Therapeutic application of intracavernosal HUCB-MNCs is a novel approach for the rat model of post-5ARI ED. Lack of serum and tissue dihydrotestosterone measurements, vehicle injections and characterization of the cells remain limitations of our study.
The persistent ED after prolonged administration of dutasteride in rats is reversed by HUCB-MNC treatment, which holds promise as a realistic therapeutic modality for this type of ED.
Oztekin CV, Yilmaz-Oral D, Kaya-Sezginer E, et al. Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats. J Sex Med 2021;18:889–899.
The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia
2018, Asian Journal of Urology
Benign prostatic hyperplasia (BPH) is characterized by an enlarged prostate, lower urinary tract symptoms (LUTS), and a decreased urinary flow rate. Common in older men, BPH is a progressive disease that can eventually lead to complications including acute urinary retention (AUR) and the need for BPH-related surgery. Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone (DHT), which is formed from testosterone under the influence of 5-alpha reductase. Thus, 5-alpha reductase inhibitors (5-ARIs) effectively reduce the serum and intraprostatic concentration of DHT, causing an involution of prostate tissue. Two 5-ARIs are currently available for the treatment of BPH—finasteride and dutasteride. Both have been demonstrated to decrease prostate volume, improve LUTS and urinary flow rates, which ultimately reduces the risk of AUR and BPH-related surgery. Therefore, either alone or in combination with other BPH medications, 5-ARIs are a mainstay of BPH management.
Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials
2016, Journal of Sexual Medicine
5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA).
To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction.
A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests.
Sexual dysfunction, erectile dysfunction, and decreased libido.
After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48–4.42) in men with BPH and 1.21 (95% CI = 0.85–1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14–2.12) in men with BPH and 0.66 (95% CI = 0.20–2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03–2.79) in men with BPH and 1.16 (95% CI = 0.50–2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed.
Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.
Side effects of 5-alpha reductase inhibitors: A comprehensive review
2013, Sexual Medicine Reviews
Citation Excerpt :
5ARIs have a recognized, consistent association with sexual AEs, including decreased libido, erectile dysfunction (ED), and ejaculatory dysfunction (EjD). Among 27 RCTs reviewing the use of 5ARIs, reported ranges of decreased libido, ED, and EjD vary widely: drug: libido (0–65.4%), ED (0–67.4%), and EjD (0–60.4%); placebo: libido (0–59.6%), ED (0–61.5%), and EjD (0–47.3%) [12,13,15-18,31-51]. These widely discrepant results for both drug and placebo reflect differences in patient populations and study methodology.
5α‐reductase inhibitors (5ARI) include finasteride and dutasteride, and are commonly prescribed in the treatment of benign prostatic hyperplasia and androgenic alopecia. 5ARIs are associated with several known adverse effects (AEs), with varying reported prevalence rates.
The aim was to review and summarize findings from published literature detailing AEs associated with 5ARI use. A secondary aim was to review potential mechanisms of action, which may account for these observed and reported AEs.
A PubMed search was conducted on articles published from 1992 to 2012, which reported AEs with 5ARIs. Priority was given to randomized, placebo‐controlled trials. Studies investigating potential mechanisms of action for 5ARIs were included for review.
AE data reported from available trials were summarized and reviewed.
Reported AEs with 5ARIs include sexual dysfunction, infertility, mood disorders, gynecomastia, high‐grade prostate cancer, breast cancer, and cardiovascular morbidity/risk factors, although their true association, prevalence, causality, and clinical significance remain unclear. A pooled summary of all randomized, placebo‐controlled trials evaluating 5ARIs (N = 62,827) revealed slightly increased rates over placebo for decreased libido (1.5%), erectile dysfunction (ED) (1.6%), ejaculatory dysfunction (EjD) (3.4%), and gynecomastia (1.3%). The limited data available on the impact of 5ARIs on mood disorders demonstrate statistically significant (although clinically minimal) differences in rates of depression and/or anxiety. Similarly, there are limited reports of reversible, diminished fertility among susceptible individuals. Post‐marketing surveillance reports have questioned the actual prevalence of AEs associated with 5ARI use and suggest the possibility of persistent symptoms after drug discontinuation. Well‐designed studies evaluating these reports are needed.
5ARIs are associated with slightly increased rates of decreased libido, ED, EjD, gynecomastia, depression, and/or anxiety. Further studies directed at identifying prevalence rates and persistence of symptoms beyond drug discontinuation are required to assess causality. Trost L, Saitz TR, and Hellstrom WJG. Side effects of 5‐alpha reductase inhibitors: A comprehensive review. Sex Med Rev 2013;1:24–41.
Androgen deprivation therapy in prostate cancer: Focusing on sexual side effects
2012, Journal of Sexual Medicine
Citation Excerpt :
The clinical studies that reported increased incidence of ED in patients taking finasteride (5 mg or 1 mg/day) did not either assess the baseline sexual function or use a validated questionnaire [102-104]. The ED occurred predominantly during the first year of therapy and subsequently by the end of 3–7 years of therapy it resolved completely in half of the patients [99,105,106]. In almost all the studies, the prevalence of ED declined with increased duration of therapy.
Androgen deprivation therapy (ADT) is the cornerstone in the treatment of advanced and metastatic prostate cancer (PC). However, recent publications suggest that ADT may increase cardiovascular (CV) problems (morbidity and mortality), most probably because androgens regulate fat distribution, insulin sensitivity, and lipid metabolism.
The aim of the present review is to analyze different modalities of ADT, emphasizing advantages and possible related adverse sexual events.
A systematic search of published evidence was performed using Medline (from 1969 to September 2011).
The most important studies regarding the relationship among testosterone, PC, and the role of ADT were reviewed.
There is unequivocal evidence that reducing androgen signaling to the hypogonadal range can reduce PC growth and patient symptoms; however, androgen dependency of prostate growth is evident only in the hypogonadal condition but not in the eugonadal state (the “saturation hypothesis”). There is clear evidence that ADT improves disease‐free and overall survival only under two conditions: (i) in combination with primary radiation for locally advanced or high‐risk diseases and (ii) as an adjuvant therapy for positive lymph node diseases after prostatectomy. On the other hand, it should be recognized that ADT can adversely affect not only traditional CV risk factor (including serum lipoproteins, insulin sensitivity, and obesity) but also sexual life, being associated with reduced libido and erectile, ejaculatory, and orgasmic disorders.
Physicians should weigh the risk/benefit ratio before prescribing ADT. Corona G, Gacci M, Baldi E, Mancina R, Forti G, and Maggi M. Androgen deprivation therapy in prostate cancer: Focusing on sexual side effects. J Sex Med 2012;9:887–902.

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^∗: Members of the Finasteride Study Group are listed in the Appendix, pp 293–294.

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Rapid communicationThree-year safety and efficacy data on the use of finasteride in the treatment of benign prostatic hyperplasia

Abstract

J Urol

J Urol

J Urol

J Urol

Nonoperative management of benign prostatic hyperplasia

J Urol

Mortality and reoperation after open and transurethral resection of the prostate for benign prostatic hyperplasia

N Engl J Med

Outcome analysis after treatment for benign prostatic hyperplasia (BPH) by various modalities: confidence profile analysis

J Urol (Abstr. 606)

Steroid 5a-reductase deficiency in man: an inherited form of male pseudohermaphroditism

Science

Rapid communication
Three-year safety and efficacy data on the use of finasteride in the treatment of benign prostatic hyperplasia